European Journal of Heart Failure (2014) 16, 103111

doi:10.1002/ejhf.30

Co-morbidities in patients with heart failure:

an analysis of the European Heart Failure Pilot
Survey
Vincent M. van Deursen1, Renato Urso2, Cecile Laroche3, Kevin Damman1,
Ulf Dahlstrm4, Luigi Tavazzi5, Aldo P. Maggioni6, and Adriaan A. Voors1,*
1 Department

of Cardiology, University of Groningen, Groningen, The Netherlands; 2 Pharmacology Unit Giorgio Segre, University of Siena, Siena, Italy; 3 EORP Department,
ESC, Sophie Antipolis, France; 4 Department of Cardiology, Linkoping University Hospital, Linkoping, Sweden; 5 GVM Care and Research, Ettore Sansavini Health Science
Foundation, Maria Cecilia Hospital, Cotignola, Italy; and 6 ANMCO Research Center, Florence, Italy

Received 27 March 2013; revised 6 June 2013; accepted 14 June 2013

Aims

Co-morbidities frequently accompany heart failure (HF), contributing to increased morbidity and mortality, and an
impairment of quality of life. We assessed the prevalence, determinants, regional variation, and prognostic implications
of co-morbidities in patients with chronic HF in Europe.
.....................................................................................................................................................................
Methods
A total of 3226 European outpatients with chronic HF were included in this analysis of the European Society of
and results
Cardiology (ESC) Heart Failure Pilot Survey. The following co-morbidities were considered: diabetes, hyper- and
hypothyroidism, stroke, COPD, sleep apnoea, chronic kidney disease (CKD), and anaemia. Prognostic implications of
co-morbidities were evaluated using population attributable risks (PARs), and patients were divided into geographic
regions. Clinical endpoints were all-cause mortality and HF hospitalization. The majority of patients (74%) had a least
one co-morbidity, the most prevalent being CKD (41%), anaemia (29%), and diabetes (29%). Co-morbidities were
independently associated with higher age (P < 0.001), higher NYHA functional class (P < 0.001), ischaemic aetiology of
HF (P < 0.001), higher heart rate (P = 0.011), history of hypertension (P < 0.001), and AF (P < 0.001). Only diabetes,
CKD, and anaemia were independently associated with a higher risk of mortality and/or HF hospitalization. There
were marked regional differences in prevalence and prognostic implications of co-morbidities. Prognostic implications
of co-morbidities (PARs) were: CKD = 41%, anaemia = 37%, diabetes = 14%, COPD = 10%, and <10% for all other
co-morbidities.
.....................................................................................................................................................................
Conclusion
In this pilot survey, co-morbidities are prevalent in patients with chronic HF and are related to the severity of the
disease. The presence of diabetes, CKD, and anaemia was independently related to increased mortality and HF
hospitalization, with the highest PAR for CKD and anaemia.

..........................................................................................................
Heart failure Co-morbidities Prognosis

Introduction
Heart failure is characterized by high morbidity and mortality
and a poor quality of life.1 There is growing awareness that
co-morbidities frequently accompany heart failure and lead to
increased morbidity and mortality, and a further decrease in quality
of life.2 6 The prevalence of co-morbidities is higher in patients

....................

Keywords

with more severe signs of heart failure.5,6 This suggests either

common aetiological factorssuch as age and cardiovascular risk
factorsor a causal relationship with heart failure. However,
determinants of multiple co-morbidities remain unknown.
While numerous studies focus on a single co-morbidity, only
few studies have examined multiple non-cardiac co-morbidities in
patients with heart failure.5,7,8 In a cross-sectional study of 122 630

*Corresponding author. Department of Cardiology, University Medical Center Groningen Hanzeplein 1, 9700 RB Groningen, The Netherlands. Tel: +31 503 612 355, Fax: +31
503 614 391, Email: a.a.voors@umcg.nl

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European Journal of Heart Failure 2013 European Society of Cardiology

104

Methods
The HF Pilot Survey of the EURObservational Research Programme
(EORP) of the European Society of Cardiology (ESC) was a prospective, multicentre, observational survey.9 The aim was to include a
broad spectrum of patients with heart failure from outpatient clinics and those admitted to a hospital. Outpatients were diagnosed
with chronic heart failure according to the clinical judgement of a
cardiologist. Admitted patients had pre-existing heart failure or newonset heart failure requiring i.v. therapy. A total of 5118 patients were
included, 1892 (37%) in-hospital patients with acute heart failure and
3226 (63%) outpatients with chronic heart failure, recruited from 136
cardiology centres in 12 European countries. These countries were
selected on the basis of previous performances in the Euro Heart Surveys and geographical distribution. The National Cardiology Societies
of each country agreed to participate in the programme and were asked
to select hospitals of different levels of complexity. The aim was to
involve a broad spectrum of cardiology units. The number of participating centres for each country was decided according to the number
of inhabitants of that country. We used all 3226 outpatients to obtain
a representative chronic heart failure population for analysis.

Regions
Four geographical regions were defined as follows: Western European
countries [Austria (n = 86), France (n = 37), Germany (n = 138), and
The Netherlands (n = 76)], Eastern European countries [Romania (n =
120) and Poland (n = 243)], Southern European countries [Greece (n
= 115), Italy (n = 1387), and Spain (n = 532)), and Northern European
countries [Denmark (n = 174), Norway (n = 126), and Sweden (n =
201)].

Co-morbidities
Co-morbidities were determined based on the case record form
as assessed by the treating physician. We used all non-cardiac comorbidities that were assessed in this survey. Co-morbidities consisted
of diabetes (n = 3223), thyroid dysfunction (n = 3171), stroke (n =
3206), COPD (n = 3202), sleep apnoea (either in medical history or
self-reported, n = 3197), chronic kidney disease [CKD; defined as
estimated GFR (eGFR) <60 mL/min/1.73 m2 , as well as eGFR on a
continuous scale, n = 2547], and anaemia [using the World Health
Organization definitions of haemoglobin <13 g/L (8.1 mmol/L) in men
and <12 g/L (7.5 mmol/L) in women, as well as haemoglobin on a
continuous scale, n = 2522]. The number of co-morbidities per patient
was also assessed. No additional diagnostic tests were performed to
determine the presence of specific co-morbidities.

........................................................................................................................................................................

elderly (>65 years) patients with heart failure, the prevalence of comorbidities was 96%.5 It was calculated that patients with >5 comorbidities are responsible for 81% of all hospital days experienced
by all heart failure patients. However, regional differences have not
been studied and determinants of multiple co-morbidities remain
unknown.
The present study examines multiple co-morbidities in a broad
spectrum of patients with chronic heart failure. We focus on
the prevalence, determinants, regional variation, and prognostic
implications of co-morbidities in a broad spectrum of patients with
chronic heart failure in Europe.

V. M. van Deursen et al.

Endpoints
To study the prognostic association with co-morbidities, all-cause
mortality and heart failure hospitalization were assessed, with a median
follow-up of 364 (335367) days.

Statistical analyses
Data are presented as the mean standard deviation (SD) for continuous variables, and as frequencies and percentages for categorical
variables. Categorical variables were compared using 2 tests. Continuous variables were compared using Students t-test.
Cox proportional hazards models were used to estimate hazard
ratios (HRs) for all-cause mortality and heart failure hospitalizations. In
multivariate multivariable analyses, the following variables with significant univariable associations with outcome at P 0.10 were included
in the model: age, sex, aetiology, hypertension, AF, congestion, body
surface area, systolic blood pressure, and heart rate. Furthermore,
we calculated the incremental value of each co-morbidity by means
of the integrated discrimination index (IDI) and net reclassification
index (NRI) for the final multivariate model vs. this model plus the
co-morbidity.
Population attributable risks (PARs) were computed as confirmatory
analyses using the package epiR. The estimated attributable fraction in
the population was reported with 95% confidence intervals (CIs). The
attributable fraction is the proportion of deaths in the population that
is attributable to the co-morbidity, as previously used by Yusuf et al.10
A P-value of <0.05 was considered statistically significant. All
tests were two-sided. The statistical analyses were performed at the
ANMCO Research Center, Florence, Italy, on behalf of the ESC, with
R (version 2.14.0).

Results
The mean age of the 3226 included patients was 66 14 years,
and 70% were men. Most patients were in NYHA class II or III (56
and 26%) and 41% had an ischaemic cause of heart failure. Table 1
shows other baseline characteristics of the study cohort.

Prevalence of co-morbidities
Of all patients, 74% had at least one co-morbidity. CKD (41%),
anaemia (29%), and diabetes (29%) were the co-morbidities with
the highest prevalence (Table 1). COPD (15%) and stroke (11%)
were also common. Sleep apnoea had a prevalence of 4%. Hypothyroidism (9%) was more prevalent than hyperthyroidism (3%). Of
all patients, only 26% (n = 610) had no co-morbidity, 30% had one
co-morbidity, 23% had two co-morbidities, and 43% had two or
more co-morbidities. Patients with reduced LVEF (n = 1580) had a
similar prevalence of co-morbidities compared with patients with
preserved LVEF (n = 1249) (Table 2).

Characteristics of patients with multiple

co-morbidities
Patients with co-morbidities were older (P < 0.001) and had a
higher NYHA class (P < 0.001). When multiple co-morbidities
were present, patients were more likely to have heart failure due to
ischaemic aetiology (P < 0.001) with hypertension (P < 0.001) and
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Co-morbidities in heart failure

Table 1 Baseline characteristics, according to patients with zero or one co-morbidity and patients with more than
one co-morbidity
All patients
1 co-morbidiy
>1 co-morbidity
P-value
(n = 3226)
(n = 1417)
(n = 1167)
...........................................................................................................................................
Age (years)
Male sex (%)
Body mass index (kg/m2 )
NYHA class
I (%)
II (%)
III (%)
IV (%)
SBP (mmHg)
Heart rate (b.p.m.)
Elevated JVP
Oedema
Ischaemic aetiology (%)
ICD/CRT(D) (%)
Hypertension (%)
History of AF (%)
Medication use
ACE-I/ARBs
Beta-blockers
Diuretics
Aldosterone blockers
Co-morbidities
Chronic kidney disease
eGFR
Anaemia
Haemoglobin
Diabetes
COPD
Stroke
Sleep apnoea
Hypothyroidism
Hyperthyroidism

<0.001
0.02
0.12
<0.001

66 14
2268 (70)
28 5

63 14
1029 (73)
28 5

71 11
797 (68)
28 5

511 (16)
1797 (56)
854 (26)
56 (2)
125 20
72 14
242 (8)
592 (19)
1305 (41)
745 (23)
1875 (58)
1289 (40)

299 (21)
828 (59)
277 (20)
11 (1)
125 20
72 15
90 (6)
237 (17)
499 (35)
110 (8)
733 (52)
486 (34)

103 (9)
600 (52)
431 (37)
28 (2)
125 21
72 13
105 (9)
276 (24)
556 (48)
122 (10)
787 (68)
586 (50)

0.62
0.17
0.01
<0.001
<0.001
0.02
<0.001
<0.001

2833 (89)
2774 (87)
2649 (83)
1396 (44)

1280 (91)
140 (88)
1088 (77)
595 (42)

992 (86)
962 (83)
1041 (90)
527 (46)

<0.001
<0.001
<0.001
0.10

1035 (41)
68 26
727 (29)
13.4 1.9
934 (29)
484 (15)
337 (11)
128 (4)
272 (9)
101 (3)

211 (15)
79 23
124 (9)
14.1 1.5
165 (12)
75 (5)
52 (4)
19 (1)
37 (3)
21 (2)

780 (73)
54 22
589 (55)
12.6 1.9
697 (54)
363 (31)
244 (21)
104 (9)
199 (18)
68 (6)

<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001

AF (P < 0.001). Although more frequently treated with diuretics

(P < 0.001), patients with multiple co-morbidities received less
ACE inhibitor, ARB, and beta-blocker therapy (all P < 0.001).
Of all patients without co-morbidities, 15% had clinical signs
of congestion [elevated jugular venous pressure (JVP) >6 cm or
peripheral oedema]; of all patients with one, two, three, or 4 comorbidities, 24, 27, 33, and 36%, respectively, had clinical signs of
either elevated JVP or peripheral oedema (P < 0.001).

Co-morbidities and prognosis

Of all co-morbidities, diabetes, COPD, CKD, and anaemia were
significantly associated with all-cause mortality (Table 3). In multivariable analyses, after adjustment for other confounders, CKD
(HR 1.50, 95% CI 1.062.11, P = 0.0212), anaemia (HR 1.69, 95%
1.222.35, P = 0.0017), and diabetes (HR 1.74, 95% CI 1.282.37,

................................................

ACE-I, ACE inhibitor; CRT(D), cardiac resynchronization therapy(defibrillator); eGFR, estimated glomerular filtration rate; ICD, implantable cardioverter; JVP, jugular
venous pressure; SBP, systolic blood pressure.

2013 The Authors

European Journal of Heart Failure 2013 European Society of Cardiology

P = 0.0004) remained significantly related to all-cause mortality.

COPD (HR 1.37, 95% CI 0.961.94, P = 0.0819) was borderline
significant.
Chronic kidney disease (HR 1.59, 95% CI 1.232.06, P =
0.001), anaemia (HR 1.44, 95% CI 1.131.84, P = 0.0034), and
diabetes (HR 1.31, 95% CI 1.041.65, P = 0.0239) were also
independently associated with heart failure hospitalizations, as was
hypothyroidism (HR 1.46, 95% CI 1.062.01, P = 0.0221) (Table 4).
Confirming these findings, of all co-morbidities, the prognostic implication for the whole population was highest for CKD,
with a PAR of 41% (95% CI 2951%). In other words, 41%
(95% CI 2951%) of all-cause mortality in the population is
attributable to the co-morbidity CKD. Anaemia had the second
highest PAR of 37% (95% CI 2746%), followed by diabetes [14%
(95% CI 523%)] and COPD [95% CI 10% (316%)]. All other
co-morbidities had a mean PAR below 5% Figure 1.

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Table 2 Prevalence of co-morbidities in patients with

heart failure with reduced ejection fraction and in
patients with heart failure with preserved ejection
fraction
HFrEF
HFpEF
P-value
(LVEF <40%) (LVEF 40%)
................................................................
Chronic kidney disease
Anaemia
Diabetes
COPD
Stroke
Sleep apnoea
Hypothyroidism
Hyperthyroidism

541 (41)
349 (28)
470 (30)
255 (16)
166 (11)
69 (4)
152 (10)
54 (4)

383 (39)
306 (30)
343 (28)
173 (14)
129 (10)
49 (4)
96 (8)
32 (3)

0.381
0.130
0.191
0.101
0.892
0.578
0.062

HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with
reduced ejection fraction.

In terms of mortality, 18 patients without co-morbidities (1%),

171 patients with at least one co-morbidity (7%), including 27
patients (1%) with more than three co-morbidities, died. The NRI

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V. M. van Deursen et al.

and IDI are shown in the Supplementary material online, Tables

S1 and S2. Figure 1 shows that patients with 13 co-morbidities
have a higher mortality rate (HR 3.24, 95 CI 1.995.30, P < 0.001)
and higher rates of heart failure hospitalizations (HR 1.95, 95%
1.442.64, P < 0.001) than patients without co-morbidities.
Patients with >3 co-morbidities had an even higher mortality rate
(HR 9.33, 95% CI 5.1416.96, P < 0.001), and were re-hospitalized
more frequently (HR 4.74, 95% CI 3.107.23, P < 0.001) than
patients without co-morbidities.

Geographical regions
In Figure 2 the prevalence of co-morbidities is divided into European regions. Eastern European patients (n = 363) had less CKD
(28% vs. 39, 43, and 42%) compared with Northern (n = 501),
Southern (n = 2025), and Western (n = 337) European regions,
respectively. The prevalence of anaemia was much lower in Eastern European patients (17% vs. 29, 32, and 24%). Northern European patients had a much lower prevalence of diabetes (16%
vs. 32, 33, and 29%) compared with Southern, Western, and
Eastern European regions, respectively. Geographical differences
were minimal for hyperthyroidism, stroke, and COPD. Hypothyroidism was twice as common in Southern and Western European

Table 3 Univariate and multivariate associations between co-morbidities and all-cause mortality
No. of deaths (%)

Univariate
Multivariate
....................................
...................................
HR (95% CI)
P-value
HR (95 % CI)
P-value
...........................................................................................................................................
Chronic kidney disease
Anaemia
Diabetes
COPD
Stroke
Sleep apnoea
Hypothyroidism
Hyperthyroidism

130 (5%)
107 (4%)
90 (3%)
52 (2%)
32 (1%)
8 (0%)
27 (1%)
10 (0%)

2.77 (2.083.69)
3.12 (2.364.12)
1.57 (1.212.04)
1.76 (1.292.40)
1.35 (0.931.97)
0.85 (0.421.72)
1.47 (0.982.19)
1.41 (0.752.65)

<0.0001
<0.0001
<0.0001
<0.0001
0.1109
0.6509
0.0617
0.2915

1.50 (1.062.11)
1.69 (1.222.35)
1.74 (1.282.37)
1.37 (0.961.94)
1.20 (0.791.82)
1.00 (0.482.06)
1.31 (0.832.07)
1.16 (0.582.30)

0.0212
0.0017
0.0004
0.0819
0.3873
0.9894
0.2412
0.6720

Multivariate hazard ratios (HRs) are corrected for age, sex, aetiology, hypertension, AF, congestion, body surface area, systolic blood pressure, and heart rate per co-morbidity.
CI, confidence interval.

Table 4 Univariate and multivariate associations between co-morbidities and heart failure hospitalization
Univariate
Multivariate
...........................................
...........................................
HR (95% CI)
P-value
HR (95% CI)
P-value
...........................................................................................................................................
Chronic kidney disease
Anaemia
Diabetes
COPD
Stroke
Sleep apnoea
Hypothyroidism
Hyperthyroidism

2.16 (1.752.66)
2.12 (1.722.61)
1.47 (1.211.79)
1.45 (1.141.84)
1.17 (0.881.57)
1.22 (0.781.91)
1.66 (1.252.21)
1.20 (0.731.97)

<0.0001
<0.0001
<0.0001
0.0026
0.2844
0.3742
<0.0001
0.4753

1.59 (1.232.06)
1.44 (1.131.84)
1.31 (1.041.65)
1.09 (0.821.44)
1.09 (0.791.52)
0.94 (0.561.58)
1.46 (1.062.01)
1.07 (0.641.81)

0.0005
0.0034
0.0239
0.5745
0.5839
0.8156
0.0221
0.7877

Multivariate hazard ratios (HRs) are corrected for age, sex, aetiology, hypertension, AF, congestion, body surface area, systolic blood pressure, and heart rate per co-morbidity.
CI, confidence interval.

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Co-morbidities in heart failure

(a)

(b)

Figure 1 (A) Mortality among groups of multiple co-morbidities. Groups are defined as 0 co-morbidities, 13 co-morbidities, and >3

countries (both 10% vs. 5 and 6%). Sleep apnoea was diagnosed more often in Western European countries (10% vs. 2, 2,
and 4%).
Overall, patients from the Northern European countries had
fewer co-morbidities (72%) than those from Western European
countries (77%), followed by those from Eastern (78%) and Southern European countries (80%).

Discussion
This study examines multiple co-morbidities in a broad spectrum
of patients in chronic heart failure. In this pilot survey, we found
that the majority of patients had a least one co-morbidity, and
the number of co-morbidities increased with the severity of heart
failure. Diabetes, CKD, and anaemia had the highest prevalence

..............................................

co-morbidities. (B) Heart failure hospitalization among groups of multiple co-morbidities. Groups are defined by 0 co-morbidities, 13 comorbidities, and >3 co-morbidities.

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European Journal of Heart Failure 2013 European Society of Cardiology

and were independently associated with both mortality and heart

failure hospitalization.

Prevalence of co-morbidities
Chronic kidney disease, anaemia, and diabetes were the most
common co-morbidities in our chronic heart failure patients, along
with COPD and stroke. These findings are consistent with other
reports.11 14
In the absence of active screening, we found a much lower
prevalence for sleep apnoea in our population, in stark contrast to
the prevalence of up to 60% reported in the recent literature.15 22
This discrepancy underscores the need for better screening for
co-morbidities, particularly in cases where symptoms overlap with
those of heart failure. The same holds true for COPD, where
prevalence is reported up to 50%.23,24 In another study, only 43% of

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V. M. van Deursen et al.

patients with evidence of COPD during spirometry self-reported

having COPD.25
We found that hypothyroidism had a higher prevalence compared with hyperthyroidism. This could be due to the effect of
amiodarone therapy on thyroid dysfunction. In patients with persistent AF, hypothyroidism has been reported to have a prevalence
of 31% in those treated with amiodarone compared with 7% in the
control group.26
We found a high prevalence of co-morbidities in patients with
chronic heart failurenearly half had two or more co-morbidities.
In a cross-sectional study of 122 630 patients with heart failure,
the prevalence of co-morbidities was even higher.5 This difference
is probably due to the greater number of co-morbidities assessed
in the cross-sectional study.

Determinants of co-morbidities
The literature shows a high prevalence of co-morbidities in patients
with heart failure. Although co-morbidities might cause heart
failure, it is reasonable to believe that heart failure itself might
be a cause of multiple other co-morbidities.6 This is supported by
the finding that the prevalence of co-morbidities is associated with
the severity of heart failure, measured with the NYHA functional
classification.27 In addition to neurohormonal changes and the
negative effect of heart failure medication, haemodynamic factors
could also play a pathophysiological role.13,28 31
We found that patients with co-morbidities were older and
had more advanced heart failure, reflected by a higher NYHA

....................................................................................

Figure 2 The prevalence of multiple co-morbidities per geographical regions in Europe (East, North, South, and West).

class and a higher prevalence of hypertension and AF, although

a causal relationship cannot be established based on the data.
Patients with heart failure of ischaemic aetiology had more
co-morbidities, and patients with more co-morbidities had
more clinical signs of congestion (elevated JVP or peripheral
oedema). This is consistent with our previous findings that
congestion plays a pathophysiological role in renal and liver
dysfunction.13,31 Organs in heart failure may also be affected by
impaired haemodynamics, reflected by elevated venous pressure,
among other factors.6
Importantly, we found that patients with co-morbidities were
less likely to be receiving evidence-based therapies, such as
ACE inhibitors, ARBs, and beta-blockers. In accordance, previous
studies have shown that sicker patients are more likely to have side
effects or contraindications.32 34

Population attributable risk

The term attributable risk is the difference in the rate of a
condition (for instance mortality) between an exposed population
and an unexposed population (presence or absence of a comorbidity). Attributable risk was first described in 1953 and
has been used since.10,35 Interestingly, attributable risks combine
incidence with effect. For our analyses, PAR can be described
as the reduction in mortality that would be observed if the
population was entirely unexposed to a certain co-morbidity,
compared with the mortality pattern in patients without that comorbidity.
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When co-morbidities were considered separately, we found

that CKD and anaemia had the highest PAR. All-cause mortality
could also be attributed to diabetes and stroke, while other comorbidities lacked a significant PAR. The high PARs for CKD and
anaemia are driven by the combination of high prevalence and a
strong association with mortality.

Prognosis and co-morbidities

Previous studies have shown a strong association between comorbidities and adverse clinical outcomes.3,4,11 It has been calculated that patients with 5 co-morbidities are responsible for
81% of all hospital days experienced by all heart failure patients.5
Our findings confirm that patients with increasing numbers of comorbidities have an increasing risk of both mortality and heart
failure hospitalization.
Accordingly, we found that CKD, anaemia, and diabetes
remained significantly and independently related to all-cause
mortality and heart failure hospitalizations. This is in accordance
with other studies reporting on CKD and anaemia separately.
This supports a causal relationship between heart failure and
co-morbidities, linking them to disease severity.
Diabetes was also associated with a poorer prognosis in heart
failure. In acute heart failure, diabetic patients had worse outcome
compared with non-diabetics.36 The relationship with prognosis is
less clear in patients with chronic heart failure.37 39
Regarding sleep apnoea, we did not find an association with
outcome in the present study, although other studies show that
sleep apnoea is associated with increased mortality.40,41 We believe
that this difference can be explained by under-reporting due to
a lack of screening, as explained previously. Other studies show
that, after adjustment for confounders, sleep apnoea doubles the
mortality risk in patients with heart failure.40,41

Geographical regions
Patients from the Northern European countries were less likely to
have co-morbidities, followed by Western, Eastern, and Southern
European countries, in ascending order. This was largely driven
by diabetes, which had a low prevalence in Northern European
countries compared with the other regions. However, patients
from Eastern European countries were less likely to have CKD and
anaemia. Hypothyroidism was slightly more commonly diagnosed
in Southern and Western Europe, while sleep apnoea was more
commonly diagnosed in Western Europe.
In addition to prevalence, there were also marked regional
differences in the prognostic implications of co-morbidities. In
Eastern and Northern European patients, all-cause mortality
was less attributable to diabetes, COPD, and CKD, compared
with Southern and Western European patients. In Southern and
Northern European countries, mortality was less attributable to
stroke.

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Co-morbidities in heart failure

2013 The Authors

European Journal of Heart Failure 2013 European Society of Cardiology

Limitations
As is the case for all surveys, the voluntary participation and
recruitment of patients imposes limitations that must be acknowledged. First, as mentioned in the main article,9 this pilot study
tried to balance the methodological need for consecutive enrolment with the practical feasibility by reducing the workload for
centres with limited recruitment to 1 day per week for 8 months.
Secondly, the study population may not represent the general heart
failure population. Participating centres were selected proportionally to the size of the population of the participating countries,
accounting for the different technological levels of the cardiology
centres invited to participate. Another important limitation is that
the diagnosis of heart failure was made by the treating physician,
and both diagnosis and events were not adjudicated.
There are many potential explanations for the regional differences observed. These include a lack of screening for comorbidities in various regions of Europe, or imperfect representativeness of the regional populations. Hospital care practices also
differ between countries and centres. However, the observed differences may also be real and thus related to the heterogeneous
European epidemiology, with regional variation in prevalence, cardiovascular risk factors, and cardiovascular event rates.42

Conclusion
This is the first study to examine multiple co-morbidities in a broad
spectrum of patients with chronic heart failure. This pilot survey
showed that the majority of patients had a least one co-morbidity,
with CKD, anaemia, and diabetes being most prevalent, and that
the number of co-morbidities increased with the severity of heart
failure. Diabetes, CKD, and anaemia were independently associated
with both mortality and HF hospitalization. However, there were
marked differences in prevalence and prognostic implications of comorbidities across various European regions.

Funding
The Survey was funded by the ESC. No industrial support was used.
Each participating National Cardiology Society was granted 10
000 to help with the organizational needs regarding the national
network implementation. At present, the following companies are
supporting the EURObservational Research programme: GOLD:
Boehringer Ingelheim International, Menarini International, SanofiAventis Group, Laboratoires Servier; SILVER: Amgen; BRONZE:
Boston Scientific International.
Conflicts of interest: A.A.V. received consultancy fees and/or
research grants from Alere, Bayer, Cardio3Biosciences, Celladon,
Ceva, Novartis, Servier, Torrent, and Vifor; is a Clinical Established Investigator of the Dutch Heart Foundation (2006T37); is
supported by a grant from the Dutch Heart Foundation entitled: Approaching Heart Failure by Translational Research of RNA
mechanisms (ARENA); and is leader of a project funded by the
European Commission (FP7-242209-BIOSTAT-CHF), entitled: a
systems BIOlogy Study to TAilered Treatment in Chronic Heart

110

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